Crystalline menaphthyl quaternary ammonium salts



Patented June 8, 1954 UNITED STATES PATENT OFFICE CRYSTALLINE MENAPHTHYLQUATERNARY AMMONIUM SALTS No Drawing. Application September 11, 1952,Serial No. 309,146

6 Claims. 1

This invention relates to the preparation of a new class of quaternaryammonium organic compounds. More particularly, it concerns novelcrystalline germicides which are quaternary ammonium chlorides.

The need for crystalline germicides possessing high bacteriologicalactivity has long been recognized, but a satisfactory material has notheretofore been developed. Useful germicides of such a type must possessmany special properties, which up to now have not been found together inone product. The material should first and foremost be crystalline;anhydrous powders are most easily, safely and cheaply packaged andhandled. Such a product should also be watersoluble and non-hygroscopic;germicides are normally employed in aqueous systems, but at the sametime they should not readily pick up moisture during storage andshipment. A germicide must also, very obviously, have highbacteriological activity, generally measured by its phenol coefiicient.For safetys sake, too, it is particularly desirable to have the materialnon-irritant to the skin, eyes, mucous membranes, etc. Lack of odor andcolor are also advantageous. Further, to be commercially practicable agermicide should be easily prepared from readily available andcomparatively inexpensive raw materials.

There is in effect only one solid quaternary ammonium germicidecurrently enjoying some commercial use: an isooctylphenoxyethoxyethylbenzyl ammonium chloride. This has the advantage of being solid, ofcourse. Too, it has a fairly satisfactory phenol coefiicient, althoughconsiderably lower than that of conventional non-solid germicides (i. e.about 325 with S. Aureus and 200 with Sal. typhosa). However, it ishygroscopic and markedly irritating to mucous membranes. Another type ofsolid quaternary ammonium compounds is known, namely certain bromides.However, these are so hygroscopic that they are most difiicult to obtainin solid form, they are so expensive that they do not compete withstandard germicides, and finally their germicidal activity is in facttoo low to render them of interest in the field.

A novel class of quaternary ammonium products has now been preparedwhich obviate the above and other disadvantages of hitherto knowncompounds. This new class comprises crystalline, non-hygroscopic,bacteriologically active n-alkyl dimethyl alpha-menaphthyl ammoniumchlorides wherein the alkyl group contains substantially between ten andfourteen carbon atoms.

powders, suitable for relatively cheap packaging, long storage, and safehandling. Particularly good examples of this class are the n-decyl,lauryl (n-dodecyl) and n-tetradecyl compounds. Of these, lauryl dimethylalpha-menaphthyl ammonium chloride is especially preferred by reason ofits unusually high phenol coeflicient and its ease of preparation.

Representative bacteriological activity of some of these materials inrelation to two standard microorganisms is as follows: (According to themethod given by the U. S. Department of Agriculture Bulletin No. 198.)

Phenol Coelficient at 20 C.

Alkyl group m S. aureus Sal. typhosa The peak of efficiency in thisseries is thus reached by the lauryl compound.

The unique character of the new germicides is further shown by the factthat closely related quaternary ammonium compounds do not exhibit at allsimilar properties. Peculiarly enough, even isomers or homologues of theproducts have been obtained only as very hygroscopic, syrupy materials,non-crystalline in character and most difficult to handle. This is true,for instance, of lauryl dimethyl beta-menaphthyl ammonium chloride,lauryl dimethyl (beta-methyl alphamenaphthyl) ammonium chloride, andlauryl dimethyl (tetrahydro alpha-menaphthyl) ammonium chloride.

The process whereby the valuable products of this invention are obtainedbroadly comprises heating together in an inert liquid systemalphachloromethyl naphthalene and a n-alkyl dimethyl amine wherein thealkyl group contains substantially between ten and fourteen carbonatoms, e. g. n-decyl dimethyl amine, n-dodecyl dimethyl amine,n-tetradecyl dimethyl amine, mixtures thereof or the like. The liquidsystem may comprise certain organic solvents in which the reactants aresoluble, such as alcohol, dioxane, acetone, benzene, ethyl acetate,carbon tetrachloride, etc. However, this is not necessary and the systemmay be one, like water, in which the reactants themselves are insolublebut the reaction product is appreciably soluble. Preferably, of course,the product is soluble in the particular liquid system only at theelevated temperatures achieved by the reaction, and grows appreciablyinsoluble therein as the mass is thereafter cooled, say to merely roomtemperature or to an easily obtainable lower temperature. Rapidcrystallization of the product from solution is thereby achieved. Whenreaction occurs between the two organic constituents a solution isformed in the system, which is then cooled. The resulting precipitate ofcrystalline n-alkyl dimethyl alpha-menaphthyl ammonium chloride isfinally recovered.

According to a preferred embodiment of this process, alpha-chloromethylnaphthalene is heated in an aqueous medium with a n-alkyl dimethylamine, such as lauryl dimethyl amine (the lauryl group Originating fromcocoanut fatty acids). Although not essential, it is obviously best forcomplete reaction and optimum efficiency to employ stoichiometricequivalents of the two reactants. The mixture is stirred mechanicallyfor intimate contact while being heated. When the temperature has risensufliciently (to about 50 C. in the case of the lauryl compound) thereaction becomes exothermic and the constituents dissolve in the mediumto form a clear solution. The operation may be stopped at this point, ifdesired. However, to insure full utilization of the reactants andadequate product yields, it is preferable to keep the temperature atjust below the boiling point of the system for some additional time, sayto 3 hours. The time required for complete reaction is readilydetermined, inter alia, by titrating a sample of the solution withsilver nitrate to indicate when the available chlorine has beenconverted to the chloride ion. one skilled in the art can thus easilyestablish the time best suited for a given reaction, depending upon theparticular reactants and system employed, the temperature, and suchinterdependent operating conditions.

When the reaction has terminated, the quaternary ammonium product may berecovered from solution by substantially any desired means, e. g. bysimple evaporation of the solvent, cooling until the precipitate beginsto salt out, seeding with crystals of preformed product, or acombination of these techniques. An especially satisfactory method is toraise the temperature to the boiling point of the system, so that themixture is first concentrated. Steam-distillation is frequentlyemployed, whereby byproducts and any unreacted materials, as well as thesolvent, may be removed. The residue is finally allowed to cool, and theproduct begins to crystallize out. This cooling may be simply to roomtemperature or, to speed the precipitation, the mass may be refrigeratedat below room temperatures, e, g. to 15 C. To speed crystallizationstill more, previously obtained crystals of the same quaternary ammoniumcompound may be used to seed the solution.

The precipitated crystals of the new germicide may finally be recoveredfrom the mother liquor by any desired means. Filtration is particularlyeasy and rapid, especially in an aqueous system, although sometimes thefiltrate may foam considerably. The crystals may finally be washed orotherwise further purified and/or recrystallized, if thought desirable.A free flowing, anhydrous, non-hygroscopic powder is obtained.

As already mentioned, the new products of this invention have a numberof distinctive advantages not heretofore contemplated in germicides.Among these may be mentioned especially the facts that they are:

l. Easily prepared from commercially available and relativelyinexpensive raw materials.

2. Easily isolated in solid, crystalline form. 3. Non-hygroscopic,water-soluble and non- 5 irritant.

4. Generally colorless and odorless.

5. Bacteriologically active, being actually superior in this property tomost commercially available germicides.

The following examples are given simply to illustrate this invention andnot in any way to limit its scope. Indeed, as many apparently widelydifferent embodiments of this invention may be made without departingfrom the spirit and scope hereof, it is to be understood that the aboveinvention is not limited except as defined in the appended claims.

Example One hundred and seventy-four grams (1.0 mol) of alphachloromethyl naphthalene and 242 grams (1.0 mol) of lauryl dimethylamine were mixed with 1230 grams of water, and the milky mixture washeated under refiux with mechanical stirring. When the temperaturereached 50 C., the reaction became exothermic and a clear solution wasformed. Heating was continued for one hour at 60-65. After this period,titration with silver nitrate indicated that the available chlorine hadbeen quantitatively converted to chloride ion. One thousand grams ofwater were added, and the temperature of the mixture was raised to theboiling point. Steam distillation removed a small but significant amountof oil. The residual solution was allowed to cool to room temperatureand seeded with a few crystals of lauryl dimethyl alpha-menaphthylammonium chloride, to accelerate crystallization. A white solid began toform. The mass was further cooled in a refrigerator (at about 15 C. forsix hours, and the precipitate was then filtered on a Buchner funnel anddried. Filtration was very easy and rapid, except for considerablefoaming of the filtrate.

Crystals of lauryl dimethyl alpha-menaphthyl ammonium chloride were thusobtained as a freefiowing white powder, practically odorless andnon-hygroscopic. This product contained the calculated amount oftitratable chloride (8.4% as 01'') and melted at 77-80 C. The yield was564 grams, or 90% of the theoretical. Titration of the filtrateindicated that the aqueous solution (presumably saturated) contained 3%dissolved product, thus accounting for a further 8% of the theoreticalyield, and bringing the total recovery up to 98% of the theory. The newcrystalline quaternary ammonium germicide exhibited the followingsolubility characteristics.

Solvent At B. P.

Ethanol Dioxane Carbon tetrachloride very sol. very sol. very sol. verysol. very sol. very sol. insol very sol.

5 cally active n-alkyl dimethyl alpha-menaphthyl ammonium chlorideswherein the alkyl group contains between 10 and 14 carbon atoms.

2. Crystalline, non-hygroscopic, bacteriologically active lauryldimethyl alpha-menaphthyl ammonium chloride.

3. A process which comprises heating together in a liquid systemalpha-chloromethyl naphtha-- lene and a n-alkyl dimethyl amine whereinthe alkyl group contains between 10 and 14 carbon atoms, cooling thesystem, and recovering the resulting precipitate of crystalline n-alkyldimethyl alpha-menaphthyl ammonium chloride.

4. A process which comprises heating an aqueous mixture of equimolarproportions of alphachloromethyl naphthalene and lauryl dimethyl amineat least until a clear solution is obtained, steam-distilling thesolution, cooling the resulting concentrate to at least roomtemperature, and recovering the crystalline lauryl dimethyl alpha- 6menaphthyl ammonium chloride thereby precipitated.

5. Crystalline, non-hygroscopic, bacteriologically active n-decyldimethyl alpha-menaphthyl ammonium chloride.

6. Crystalline, non-hygroscopic, bacteriologically active n-tetradecyldimethyl alpha-menaphthyl ammonium chloride.

References Cited in the file of this patent UNITED STATES PATENTS NumberName Date 2,309,592 Hueter Jan. 26, 1943 OTHER REFERENCES Baltzly: J. A.C. 8., vol. 64, Sept. 1942, p. 2231.

Braun: Ber. deut. Chem, vol. 56 (1923), p. 2171.

Winternitz et al.: Bull. Soc. Chim. Biol., vol.

1. CRYSTALLINE, NON-HYGROSCOPIC, BACTERIOLOGICALLY ACTIVE N-ALKYLDIMETHYL ALPHA-MENAPHTHYL AMMONIUM CHLORIDES WHEREIN THE ALKYL GROUPCONTAINS BETWEEN 10 AND 14 CARBON ATOMS.